Author:
Arnold Alan A,Aboukameel Amro,Chen Jianyong,Yang Dajun,Wang Shaomeng,Al-Katib Ayad,Mohammad Ramzi M
Abstract
Abstract
Elevated expression of anti-apoptotic Bcl-2 family proteins have been linked to a poor survival rate of patients with Follicular Lymphoma (FL). This prompted us to evaluate a very potent non-peptidic Small-Molecule Inhibitor (SMI) targeting Bcl-2 family proteins, Apogossypolone (ApoG2) using follicular small cleaved cell lymphoma cell line (WSU-FSCCL) and cell isolated from lymphoma patients. ApoG2 inhibited the growth of WSU-FSCCL significantly with a 50% growth inhibition of cells (IC50) of 109 nM and decreased cell number of fresh lymphoma cells. ApoG2 activated caspases-9, -3, and -8, and the cleavage of Poly (ADP-ribose) polymerase (PARP) and Apoptosis Inducing Factor (AIF). In the WSU-FSCCL-SCID xenograft model, ApoG2 showed a significant anti-lymphoma effect, with %ILS of 84% in the intravenous and 63% in intraperitoneal treated mice. These studies suggest that ApoG2 can be an effective therapeutic agent against FL.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Molecular Medicine
Reference39 articles.
1. Rogers B: Looking at lymphoma and leukemia. Nursing. 2005, 35 (7): 56-63; quiz 63-4.
2. Ganti AK, Bociek RG, Bierman PJ, Enke CA, Vose JM, Armitage JO: Follicular lymphoma: expanding therapeutic options. Oncology (Williston Park). 2005, 19 (2): 213-28; discussion 228, 233-6, 239.
3. Fisher RI, LeBlanc M, Press OW, Maloney DG, Unger JM, Miller TP: New treatment options have changed the survival of patients with follicular lymphoma. J Clin Oncol. 2005, 23 (33): 8447-8452.
4. Sacchi S, Pozzi S, Marcheselli L, Bari A, Luminari S, Angrilli F, Merli F, Vallisa D, Baldini L, Brugiatelli M: Introduction of rituximab in front-line and salvage therapies has improved outcome of advanced-stage follicular lymphoma patients. Cancer. 2007, 109 (10): 2077-2082.
5. Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, Leblanc M, Fisher RI: Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin's lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911. J Clin Oncol. 2006, 24 (25): 4143-4149.
Cited by
72 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献